Vector-borne diseases cause over one million deaths annually in people worldwide. The long term objective of this research is to develop strains of vector mosquitoes that are genetically refractory to the transmission of pathogens such as those that cause malaria and dengue fever. These insects will be used to test the hypothesis that an increase in the frequency of a gene or allele that confers decreased vector competence to a population of mosquitoes will lead to a reduction in the incidence and prevalence of that disease. Following the successful efforts of our laboratory and others demonstrating the possibilities for engineering synthetic effector genes that produce pathogen refractory phenotypes in mosquitoes, we now propose to investigate specific drive mechanisms that would facilitate the safe and efficient spread of such genes in vector mosquito populations. The SPECIFIC AIMS of this application have been designed to take advantage of the progress made with mosquito transgenesis and the fundamental nature of embryonic development in insects, to meet the need to research gene drive mechanisms. The SPECIFIC AIMS are to: 1) Identify the cis-acting DNA and promoter elements responsible for the specific expression patterns of the nanos (nos) orthologous genes in Anopheles gambiae, An. stephensi and Aedes aegypti; 2) Construct and test synthetic transposable elements composed of mosquito nos genes and the Mos1 and piggyBac transposons; and 3) Determine if synthetic transposons can spread in caged populations of An. gambiae and Ae. aegypti.